Induction of genetic instability by gain-of-function p53 cancer mutants

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Mutant p53 gain-of-function in cancer.

In its wild-type form, p53 is a major tumor suppressor whose function is critical for protection against cancer. Many human tumors carry missense mutations in the TP53 gene, encoding p53. Typically, the affected tumor cells accumulate excessive amounts of the mutant p53 protein. Various lines of evidence indicate that, in addition to abrogating the tumor suppressor functions of wild-type p53, t...

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Cancer-derived p53 mutants suppress p53-target gene expression—potential mechanism for gain of function of mutant p53

Tumour-derived p53 mutants are thought to have acquired 'gain-of-function' properties that contribute to oncogenicity. We have tested the hypothesis that p53 mutants suppress p53-target gene expression, leading to enhanced cellular growth. Silencing of mutant p53 expression in several human cell lines was found to lead to the upregulation of wild-type p53-target genes such as p21, gadd45, PERP ...

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Tumor suppressor p53 and its gain-of-function mutants in cancer.

Tumor suppressor p53 plays a pivotal role in tumor suppression. p53 is the most frequently mutated gene in cancer. As a transcription factor, p53 mainly exerts its role in tumor suppression through transcriptional regulation of its downstream target genes. Thus, p53 and its target genes form a complex p53 signaling pathway to regulate a wide variety of biological processes to prevent tumorigene...

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Gain of oncogenic function of p53 mutants induces invasive phenotypes in human breast cancer cells by silencing CCN5/WISP-2.

CCN5/WISP-2 is overexpressed in noninvasive breast cancer cells and tissue samples, whereas its expression is minimal or undetected in invasive conditions. CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. However, the mechanism of silencing of CCN5 during the progression of the disease has been elusive. Because p53 ...

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ژورنال

عنوان ژورنال: Oncogene

سال: 2008

ISSN: 0950-9232,1476-5594

DOI: 10.1038/sj.onc.1211023